The effects of opiates on the efficacy, toxicity, or kinetics of other drugs are investigated with a focus on hepatic metabolism. A model dye, sulfobromophtalein (BSP), a model drugs are used in rodents with morphine or methadone to study mechanisms of narcotic interaction. Narcotic-induced changes in body temperature, respiratory function (changes in blood gases), and hepatic blood flow are evaluated as mediators of altered BSP disposition. Both the brain and liver are examined to identify the site of origin of narcotic action on BSP. To predict for interactions of potential clinical significance, narcotic effect on the pharmacokinetics of lidocaine, propranolol, and antipyrine are compared. The influence of opiates on the toxicity of known hepatotoxins such as carbon tetrachloride and acetaminophen is also explored.